President Donald Trump on Saturday called for an end to Iranian Supreme Leader Ayatollah Ali Khamenei's reign, stating that it is "time to look for new leadership" as protests in the country appeared to be fading.

"The man is a sick man who should run his country properly and stop killing people," Trump said in an interview with Politico. "His country is the worst place to live anywhere in the world because of poor leadership."

The president's comments came after weeks of unrest in Iran in which thousands of protesters across the country were killed. 

Trump has repeatedly warned of possible U.S. military intervention and, earlier this week, urged Iranians to keep protesting and "take over institutions," saying "help is on its way."

A day later, Trump shifted course, saying he had been informed the killings had stopped. "The best decision he ever made was not hanging more than 800 people two days ago," Trump said Saturday when asked about the size of a potential U.S. military operation in Iran.

Trump spoke shortly after Khamenei's X account posted a series of messages accusing him of being responsible for violence and unrest in Iran.

"We find the US President guilty due to the casualties, damages, and slander he inflicted upon the Iranian nation," Khamenei wrote.

In another post, Khamenei said Trump had mischaracterized violent groups as representing the Iranian people, calling it "an appalling slander."

Trump said, in response to the posts, that Iran's rulers rely on repression and violence to govern.

"What he is guilty of, as the leader of a country, is the complete destruction of the country and the use of violence at levels never seen before," Trump said.

"In order to keep the country functioning, even though that function is a very low level, the leadership should focus on running his country properly, like I do with the United States, and not killing people by the thousands in order to keep control," he said.

"Leadership is about respect, not fear and death," Trump added.